An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications

Jiang, Yanan; Shen, Xiaopei; Zhi, Fengnan; Wen, Zhengchao; Gao, Yang; Xu, Juan; Yang, Baofeng; Bai, Yunlong

doi:10.1038/s41420-023-01558-z

Cited by 18 publications

(9 citation statements)

References 143 publications

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“…Thalidomide was indicated for treatment of leprosy (erythema nodosum leprosum), later used for the treatment of graft versus host diseases, in 1998 it was approved for multiple myeloma [26]. Arsenic trioxide was previously indicated for the treatment of syphilis, in 1994 it was approved for the treatment of acute promyelocytic leukemia [27]. The non-randomized study on arsenic trioxide is not presented here.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

Samadder

2023

Preprint

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AimThe aim of this study is to identify literature suggesting drug repurposing based on various medicines found to possess enhanced efficacy against lung cancer in humans based on pre-clinical and retrospective analysis. Often pre-clinical and retrospective study findings may deviate from the results of randomized prospective clinical studies, this study intends to identify the efficacious new drugs against lung cancer in placebo-controlled studies.MethodsA systematic review of literature was performed in PubMed database on 30thAugust 2023 without any fixed timeline with terms related to ‘drug repurposing’ and ‘Lung cancer’. Post screening of literature, the names of non-chemo drugs identified were further searched inclinicaltrials.govadditionally NCT# was searched in google scholar, in-case the trial results were not available in respective source to validate the study findings.ResultsIn PubMed 513 articles were found, 9% articles mentioned about drugs with potential efficacy against lung cancer in humans. In these 45 articles 61 non-chemo drugs were identified from specific 293 clinical studies. Among these 30 studies for 23 drugs were in advanced clinical stage and 9 non-chemo medicines were identified to have positive results in randomized controlled clinical trials, rest of the drugs failed to attend designated clinical efficacy till-date. Anti-alcoholism, anti-bacterial, anti-emetics, cox-2 inhibitors, and HMG-CoA reductase inhibitor are the drugs that could potentially effective against advanced non-small cell lung cancer.ConclusionApplying the advanced search methodology to identify drugs repurposed or approved for targeted disease. All these 9 non-chemo were screened under randomized trial and currently only one drug disulfiram was found to enhance survival and response, reduced disease progression, in advanced NSCLC originally indicated for anti-alcoholism.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

Samadder

2023

Preprint

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“…This may explain the fact that the mechanism of action of some common cancer treatments (e.g., radiation, inorganic compounds, tyrosine kinase inhibitors, monoclonal antibodies, protease inhibitors, pyrimidine analogues, alkylating agents, and anthracyclines) relies on oxidative stress and ROS-dependent apoptosis [ 286 , 287 , 288 , 289 , 290 , 291 ]. OLE and HT cytotoxic actions themselves in part depend on ROS generation [ 57 , 59 , 63 , 75 , 85 , 88 , 101 , 102 ]; moreover, 200 μM OLE reduced HIF-1α mRNA and protein levels in HNE-1 and HONE-1 nasopharyngeal cancer cell lines [ 278 ], and pro-apoptotic OLE concentration corresponding to 100 μM was able to increase ROS production in MDA-MB-231 cell line, with the maximum peak obtained after 4 h incubation [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…Low concentrations of both OLE and HT (10 μM) protected HL-60 and PBMCs from H 2 O 2 -induced DNA damage, and lymphocytes from PMA-stimulated monocyte-mediated oxidative DNA damage [ 298 ]. This piece of information sounds particularly alarming, since arsenic trioxide (As 2 O 3 ) is one of the agents utilized to treat acute promyelocytic leukemia, especially in combinatory first-line therapy, and its mechanism of action relies on ROS increase [ 289 , 290 , 291 ]. Incubation with 30 μM HT for 48 h was not sufficient to reduce viability of Hep3B cells, but significantly improved cellular antioxidant capacities [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Gervasi,

Pojero

2024

Biomedicines

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The fact that the Mediterranean diet could represent a source of natural compounds with cancer-preventive and therapeutic activity has been the object of great interest, especially with regard to the mechanisms of action of polyphenols found in olive oil and olive leaves. Secoiridoid oleuropein (OLE) and its derivative hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) have demonstrated anti-proliferative properties against a variety of tumors and hematological malignancies both in vivo and in vitro, with measurable effects on cellular redox status, metabolism, and transcriptional activity. With this review, we aim to summarize the most up-to-date information on the potential use of OLE and HT for cancer treatment, making important considerations about OLE and HT bioavailability, OLE- and HT-mediated effects on drug metabolism, and OLE and HT dual activity as both pro- and antioxidants, likely hampering their use in clinical routine. Also, we focus on the details available on the effects of nutritionally relevant concentrations of OLE and HT on cell viability, redox homeostasis, and inflammation in order to evaluate if both compounds could be considered cancer-preventive agents or new potential chemotherapy drugs whenever their only source is represented by diet.

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“…Arsenic trioxide (ATO) has been approved as a primary therapeutic agent and is often used in combination with all-trans retinoic acid (ATRA) to achieve curative outcomes for acute promyelocytic leukemia (APL) [ 19 , 20 ]. Furthermore, ATO has shown potential effects in the treatment of solid malignancies, including advanced HCC [ 21 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

Li,

Pan,

Chen

et al. 2024

Cell Death Dis

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The treatment of hepatocellular carcinoma (HCC) is particularly challenging due to the inherent tumoral heterogeneity and easy resistance towards chemotherapy and immunotherapy. Arsenic trioxide (ATO) has emerged as a cytotoxic agent effective for treating solid tumors, including advanced HCC. However, its effectiveness in HCC treatment remains limited, and the underlying mechanisms are still uncertain. Therefore, this study aimed to characterize the effects and mechanisms of ATO in HCC. By evaluating the susceptibilities of human and murine HCC cell lines to ATO treatment, we discovered that HCC cells exhibited a range of sensitivity to ATO treatment, highlighting their inherent heterogeneity. A gene signature comprising 265 genes was identified to distinguish ATO-sensitive from ATO-insensitive cells. According to this signature, HCC patients have also been classified and exhibited differential features of ATO response. Our results showed that ATO treatment induced reactive oxygen species (ROS) accumulation and the activation of multiple cell death modalities, including necroptosis and ferroptosis, in ATO-sensitive HCC cells. Meanwhile, elevated tumoral immunogenicity was also observed in ATO-sensitive HCC cells. Similar effects were not observed in ATO-insensitive cells. We reported that ATO treatment induced mitochondrial injury and mtDNA release into the cytoplasm in ATO-sensitive HCC tumors. This subsequently activated the cGAS-STING-IFN axis, facilitating CD8+ T cell infiltration and activation. However, we found that the IFN pathway also induced tumoral PD-L1 expression, potentially antagonizing ATO-mediated immune attack. Additional anti-PD1 therapy promoted the anti-tumor response of ATO in ATO-sensitive HCC tumors. In summary, our data indicate that heterogeneous ATO responses exist in HCC tumors, and ATO treatment significantly induces immunogenic cell death (ICD) and activates the tumor-derived mtDNA-STING-IFN axis. These findings may offer a new perspective on the clinical treatment of HCC and warrant further study.

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An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications

Cited by 18 publications

References 143 publications

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

A Systematic Review of Literatures: To Identify Non-Cancer Drugs Repurposed for Lung Cancer

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Arsenic trioxide augments immunogenic cell death and induces cGAS-STING-IFN pathway activation in hepatocellular carcinoma

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